Soft x-ray power diagnostics for fusion experiments at NIF, Omega, and Z facilities.

In this Review Article, we discuss a range of soft x-ray power diagnostics at inertial confinement fusion (ICF) and pulsed-power fusion facilities. This Review Article describes current hardware and analysis approaches and covers the following methods: x-ray diode arrays, bolometers, transmission grating spectrometers, and associated crystal spectrometers. These systems are fundamental for the diagnosis of ICF experiments, providing a wide range of critical parameters for the evaluation of fusion performance.

Radiation, optical, power flow, and electrical diagnostics at the Z facility: Layout and techniques utilized to operate in the harsh environment.

The Z machine is a current driver producing up to 30 MA in 100 ns that utilizes a wide range of diagnostics to assess accelerator performance and target behavior conduct experiments that use the Z target as a source of radiation or high pressures. We review the existing suite of diagnostic systems, including their locations and primary configurations. The diagnostics are grouped in the following categories: pulsed power diagnostics, x-ray power and energy, x-ray spectroscopy, x-ray imaging (including backlighting, power flow, and velocimetry), and nuclear detectors (including neutron activation). We will also briefly summarize the primary imaging detectors we use at Z: image plates, x-ray and visible film, microchannel plates, and the ultrafast x-ray imager. The Z shot produces a harsh environment that interferes with diagnostic operation and data retrieval. We term these detrimental processes "threats" of which only partial quantifications and precise sources are known. We summarize the threats and describe techniques utilized in many of the systems to reduce noise and backgrounds.

Neutron time-of-flight detectors (nTOF) used at Sandia's Z-Machine.

Neutron time-of-flight (nTOF) detectors have been used on Sandia National Laboratories' Z-Machine for inertial confinement fusion and magnetized liner fusion experiments to infer physics parameters including the apparent fuel-ion temperature, neutron yield, the magnetic-radius product (BR), and the liner rho-r. Single-paddle, dual-paddle, and co-axial scintillation nTOF detectors are used in axial lines-of-sight (LOS) and LOS that are 12° from the midplane. Detector fabrication, characterization, and calibration are discussed.

Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC).

BACKGROUND: Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. There is an unmet need for new medical treatment options for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that creates an environment favouring the formation and survival of endometriosis lesions. We have generated powerful preclinical proof-of-concept data to show that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), a non-hormonal compound previously used to treat rare metabolic disorders in children. We plan a single-arm, open-label, single site exploratory clinical trial to inform the design of a future randomised controlled trial (RCT) to determine the efficacy of DCA for the treatment of endometriosis-associated pain. METHODS: We will recruit 30 women with endometriosis-associated pain over a 6-month period. All participants will receive approximately 6.25 mg/kg oral DCA capsules twice daily for 6 weeks, with a dose increase to approximately 12.5 mg/kg twice daily for a further 6 weeks if their pain has not been adequately controlled on this dose regime and side-effects are acceptable. If pain is adequately controlled with minimal side-effects, the lower dose will be continued for a further 6 weeks. The primary objective is to determine whether it is possible to achieve acceptable recruitment and retention rates within the defined exclusion and inclusion criteria. Secondary objectives are to determine the acceptability of the trial to participants, including the proposed methods of recruitment, treatment, follow-up frequency and number of questionnaires. The recruitment rate will be determined by the proportion of patients recruited from the pool of eligible women. The retention rate will be determined by the proportion of participants who attended the final trial visit. DISCUSSION: This is a feasibility study to explore effectiveness and acceptability of the proposed field methodology (recruitment, retention, study processes and compliance with treatment). The results will be used to inform the design of a future RCT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04046081 Registered 6 August 2019.

On the 'optimal' density power divergence tuning parameter.

The density power divergence, indexed by a single tuning parameter α, has proved to be a very useful tool in minimum distance inference. The family of density power divergences provides a generalized estimation scheme which includes likelihood-based procedures (represented by choice α = 0 for the tuning parameter) as a special case. However, under data contamination, this scheme provides several more stable choices for model fitting and analysis (provided by positive values for the tuning parameter α). As larger values of α necessarily lead to a drop in model efficiency, determining the optimal value of α to provide the best compromise between model-efficiency and stability against data contamination in any real situation is a major challenge. In this paper, we provide a refinement of an existing technique with the aim of eliminating the dependence of the procedure on an initial pilot estimator. Numerical evidence is provided to demonstrate the very good performance of the method. Our technique has a general flavour, and we expect that similar tuning parameter selection algorithms will work well for other M-estimators, or any robust procedure that depends on the choice of a tuning parameter.

Arsenic Concentrations in Ground and Surface Waters across Arizona Including Native Lands.

Parts of the Southwestern United States report arsenic levels in water resources that are above the United States Environmental Protection Agency's current drinking water limits. Prolonged exposure to arsenic through food and drinking water can contribute to significant health problems including cancer, developmental effects, cardiovascular disease, neurotoxicity, and diabetes. In order to understand exposure risks, water sampling and testing has been conducted throughout Arizona. This information is available to the public through often non-overlapping databases that are difficult to access and in impracticable formats. The current study utilized a systemic compilation of online databases to compile a spreadsheet containing over 33,000 water samples. The reported arsenic concentrations from these databases were collected from 1990-2017. Using ArcGIS software, these data were converted into a map shapefile and overlaid onto a map of Arizona. This visual representation shows that arsenic levels in surface and ground water exceed the United States Environmental Protection Agency's drinking water limits for many sites in several counties in Arizona, and there is an underrepresentation of sampling in several tribal jurisdictions. This information is useful for water managers and private well owners throughout the State for determining safe drinking water sources and limiting exposure to arsenic.

A bivariate power generalized Weibull distribution: A flexible parametric model for survival analysis.

We are concerned with the flexible parametric analysis of bivariate survival data. Elsewhere, we argued in favour of an adapted form of the 'power generalized Weibull' distribution as an attractive vehicle for univariate parametric survival analysis. Here, we additionally observe a frailty relationship between a power generalized Weibull distribution with one value of the parameter which controls distributional choice within the family and a power generalized Weibull distribution with a smaller value of that parameter. We exploit this relationship to propose a bivariate shared frailty model with power generalized Weibull marginal distributions linked by the BB9 or 'power variance function' copula, then change it to have adapted power generalized Weibull marginals in the obvious way. The particular choice of copula is, therefore, natural in the current context, and the corresponding bivariate adapted power generalized Weibull model a novel combination of pre-existing components. We provide a number of theoretical properties of the models. We also show the potential of the bivariate adapted power generalized Weibull model for practical work via an illustrative example involving a well-known retinopathy dataset, for which the analysis proves to be straightforward to implement and informative in its outcomes.

The provision of seven day multidisciplinary staffing in Scottish acute medical units: a cross-sectional study.

BACKGROUND: Acute medical units (AMUs) are a central component of the admission pathway for the majority of medical patients presenting to hospital in the United Kingdom and other international settings. Detail on multidisciplinary staffing provision on weekdays and weekends is lacking. Equity of staffing across 7 days is a strategic priority for national health services in the United Kingdom. AIM: To evaluate weekday compared with weekend multidisciplinary staffing in a national set of AMUs. DESIGN: Cross-sectional survey. METHODS: Twenty-nine Scottish AMUs were identified and all were included in the study population. Data were collected by semi-structured interviews with nursing, pharmacy, therapy, non-consultant medical and consultant staff. Staffing was quantified in staff hours. A correction factor of 0.5 was applied to non-dedicated staff. The percentage of weekend/weekday staffing was calculated for each unit and the mean of these percentages was calculated to give a summary measure for each professional group. RESULTS: As a percentage of weekday staffing levels, weekend staffing across the units was 93.8% for nursing staff; 2.2% for pharmacy staff; 13.1% for therapy staff; 69.6% for non-consultant staff and 65.0% for consultant staff. CONCLUSIONS: There is a contrast between weekday and weekend staffing on the AMU, with reductions at weekends in total staff hours, the proportion of dedicated vs. undedicated staff and the seniority of nursing staff. The weekday/weekend difference was far more pronounced for allied healthcare professional staff than any other group. These findings have potential implications for patient outcomes, quality of care, hospital flow and workforce planning.

How is it best to deliver care in acute medical units? A systematic review.

The majority of medical patients presenting to hospital in the UK are cared for in acute medical units (AMUs). Such units are also increasingly present internationally. Care delivery varies across units: this review aims to examine the evidence for how best to deliver AMU care.Six electronic databases and grey literature were searched. Inclusion criteria comprised interventions applied to undifferentiated patients in AMU settings. All studies were quality assessed. A narrative approach was undertaken.Nine studies, all conducted in the UK or Ireland, evaluated 1.3 million episodes, 3617 patients and 49 staff. There was single study evidence for beneficial effects of: enhanced pharmacy care, a dedicated occupational therapy service, an all-inclusive consultant work pattern, a rapid-access medical clinic and formalized handovers. Two studies found increased consultant presence was associated with reduced mortality; one of these studies found an association with a reduction in 28-day readmissions; and the other found an association with an increased proportion of patients discharged on the day they were admitted. Three studies provide evidence of the beneficial effects of multiple interventions developed from local service reviews.Overall, the quality of the evidence was limited. This review has identified operationally relevant evidence that increased consultant presence is associated with improved outcomes of care; has highlighted the potential to improve outcomes locally through service reviews; and has demonstrated an important knowledge gap of how best to deliver AMU care. These findings have importance given the challenges acute services currently face.

Glucose >200 mg/dL during Continuous Glucose Monitoring Identifies Adult Patients at Risk for Development of Cystic Fibrosis Related Diabetes.

Rationale. Cystic fibrosis related diabetes (CFRD) is the most common comorbidity in patients with CF. In spite of increased screening, diagnosis, and treatment of CFRD, the mortality rate in patients with CFRD still far exceeds the mortality rate in those without CFRD. Guidelines suggest that screening for CFRD be performed annually using the 2-hour 75-gram oral glucose tolerance test (OGTT). Adherence to recommended screening has been poor, with only approximately one-quarter of adults with CF undergoing OGTT in 2014. Use of continuous glucose monitoring (CGM) for diagnosis may become an alternative. Objectives. Our objective was to determine whether abnormal CGM predicts subsequent development of CFRD, lung function, and body mass index (BMI) decline and increased rate of CF pulmonary exacerbations in adults with CF. Methods. In a prospective single center pilot trial from September 2009 to September 2010, 21 adult patients due for routine OGTT were recruited to complete simultaneous 3-day CGM and 2-hour 75 gram OGTT. Subsequently, clinical information was reviewed from 2008 to 2015. Conclusions. There was a moderate correlation between interpreted results of 2-hour OGTT and CGM (p = 0.03); CGM indicated a greater level of glucose impairment than OGTT. Glucose >200 mg/dL by CGM predicted development of CFRD (p = 0.0002).

X-ray power and yield measurements at the refurbished Z machine.

Advancements have been made in the diagnostic techniques to measure accurately the total radiated x-ray yield and power from z-pinch implosion experiments at the Z machine with high accuracy. The Z machine is capable of outputting 2 MJ and 330 TW of x-ray yield and power, and accurately measuring these quantities is imperative. We will describe work over the past several years which include the development of new diagnostics, improvements to existing diagnostics, and implementation of automated data analysis routines. A set of experiments on the Z machine were conducted in which the load and machine configuration were held constant. During this shot series, it was observed that the total z-pinch x-ray emission power determined from the two common techniques for inferring the x-ray power, a Kimfol filtered x-ray diode diagnostic and the total power and energy diagnostic, gave 449 TW and 323 TW, respectively. Our analysis shows the latter to be the more accurate interpretation. More broadly, the comparison demonstrates the necessity to consider spectral response and field of view when inferring x-ray powers from z-pinch sources.

A shift of thermokarst lakes from carbon sources to sinks during the Holocene epoch.

Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch. However, the same thermokarst lakes can also sequester carbon, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.

The utilization of circulating cell-free fetal DNA testing and decrease in invasive diagnostic procedures: an institutional experience.

OBJECTIVE: To characterize the patient population utilizing circulating cell-free fetal DNA (ccffDNA) testing at a large academic center and evaluate trends in the performance of invasive diagnostic procedures. STUDY DESIGN: A retrospective cohort study of all patients who underwent cell-free DNA testing from May to December 2012 was performed. RESULT: During the study period, 206 patients had cell-free DNA testing. Of those, 75% (155/206) were of ages ⩾ 35 years. Of those undergoing ccffDNA testing, 41% had positive aneuploidy screening and 38% had abnormal ultrasound findings. Only 7% of the patients with negative ccffDNA testing opted for an invasive diagnostic procedure compared with 60% with positive testing (P<0.01). The rate of invasive procedures decreased from 5.9% of all visits to the center during a similar 8-month period in 2010 to 4.1% of all visits during the study period (P<0.01). CONCLUSION: Our data suggest that ccffDNA testing leads to reduced uptake of invasive procedures.

Architecture, implementation, and testing of a multiple-shell gas injection system for high current implosions on the Z accelerator.

Tests are ongoing to conduct ~20 MA z-pinch implosions on the Z accelerator at Sandia National Laboratory using Ar, Kr, and D2 gas puffs as the imploding loads. The relatively high cost of operations on a machine of this scale imposes stringent requirements on the functionality, reliability, and safety of gas puff hardware. Here we describe the development of a prototype gas puff system including the multiple-shell nozzles, electromagnetic drivers for each nozzle's valve, a UV pre-ionizer, and an inductive isolator to isolate the ~2.4 MV machine voltage pulse present at the gas load from the necessary electrical and fluid connections made to the puff system from outside the Z vacuum chamber. This paper shows how the assembly couples to the overall Z system and presents data taken to validate the functionality of the overall system.

Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis.

BACKGROUND: Acute pulmonary exacerbations accelerate pulmonary decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response. OBJECTIVE: To test whether expression of a panel of leucocyte genes directly measured from whole blood predicts reductions in sputum bacterial density. METHODS: A previously validated 10-gene peripheral blood mononuclear cell (PBMC) signature was prospectively tested in PBMC and whole blood leucocyte RNA isolated from adult subjects with CF at the beginning and end of treatment for an acute pulmonary exacerbation. Gene expression was simultaneously quantified from PBMCs and whole blood RNA using real-time PCR amplification. Test characteristics including sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curves determined the best cut-off to diagnose a microbiological response. The findings were then validated in a smaller independent sample. RESULTS: Whole blood transcript measurements are more accurate than forced expiratory volume in 1 s (FEV(1)) or C reactive protein (CRP) alone in identifying reduction of airway infection. When added to FEV(1), the whole blood gene panel improved diagnostic accuracy from 64% to 82%. The specificity of the test to detect reduced infection was 88% and the positive predictive value for the presence of persistent infection was 86%. The area under the curve for detecting treatment response was 0.81. Six genes were the most significant predictors for identifying reduction in airway bacterial load beyond FEV(1) or CRP alone. The high specificity of the test was replicated in the validation cohort. CONCLUSIONS: The addition of blood leucocyte gene expression to FEV(1) and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.

Identification of risk factors associated with acute kidney injury in patients admitted to acute medical units.

In 2009, the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report identified significant deficiencies in the management of acute kidney injury (AKI) in hospitals in the UK. Many errors arose from failure to recognise patients with AKI and those at risk of developing AKI. Currently, there is no universally accepted risk factor assessment for identifying such patients on admission to acute medical units (AMUs). A multicentre prospective observational study was performed in the AMUs of 10 hospitals in England and Scotland to define the risk factors associated with AKI and to assess quality of care. Data were collected on consecutive acute medical admissions over two separate 24-h periods. Acute kidney injury was present in 55/316 (17.7%) patients, with sepsis, hypovolaemia, chronic kidney disease (CKD) and diabetes mellitus identified as the major risk factors. Deficiencies in patient care were identified, reinforcing the continuing need to improve the management of AKI.

Inverse Batschelet distributions for circular data.

We provide four-parameter families of distributions on the circle which are unimodal and display the widest ranges of both skewness and peakedness yet available. Our approach is to transform the scale of a generating distribution, such as the von Mises, using various nontrivial extensions of an approach first used in Batschelet's (1981, Circular Statistics in Biology) book. The key is to employ inverses of Batschelet-type transformations in certain ways; these exhibit considerable advantages over direct Batschelet transformations. The skewness transformation is especially appealing as it has no effect on the normalizing constant. As well as a variety of interesting theoretical properties, when likelihood inference is explored these distributions display orthogonality between elements of a pairing of parameters into (location, skewness) and (concentration, peakedness). Further, the location parameter can sometimes be made approximately orthogonal to all the other parameters. Profile likelihoods come to the fore in practice. Two illustrative applications, one concerning the locomotion of a Drosophila fly larva, the other analyzing a large set of sudden infant death syndrome data, are investigated.

Planar wire-array Z-pinch implosion dynamics and X-ray scaling at multiple-MA drive currents for a compact multisource hohlraum configuration.

An indirect drive configuration is proposed wherein multiple compact Z-pinch x-ray sources surround a secondary hohlraum. Planar compact wire arrays allow reduced primary hohlraum surface area compared to cylindrical loads. Implosions of planar arrays are studied at up to 15 TW x-ray power on Saturn with radiated yields exceeding the calculated kinetic energy, suggesting other heating paths. X-ray power and yield scaling studied from 1-6 MA motivates viewfactor modeling of four 6-MA planar arrays producing 90 eV radiation temperature in a secondary hohlraum.

Prevalence and time trends in diabetes and physical inactivity among adult West African populations: the epidemic has arrived.

OBJECTIVE: To determine the prevalence and distribution of, and trends in, physical inactivity and diabetes in adult West African populations. DESIGN: Systematic review and meta-analysis. METHODS: Literature searches were conducted using four electronic databases. Journal hand searches and examination of citations of relevant articles were also undertaken. To be included, studies had to be population based, use clearly defined criteria for measuring diabetes and physical inactivity, present data that allowed calculation of the prevalence of diabetes or physical inactivity, and sample adult participants. Studies retrieved were appraised critically. Meta-analysis was performed using the DerSimonian-Laird random effect model. RESULTS: Twenty-one reports were retrieved for diabetes and 15 reports were retrieved for physical in/activity. Most studies (10 for diabetes and six for physical activity) were conducted solely among urban populations. The prevalence of diabetes in West Africa was approximately 4.0% [95% confidence interval (CI) 2.0-9.0] in urban adults and 2.6% (95%CI 1.5-4.4) in rural adults, and was similar in men and women [prevalence ratio (PR) 1.36, 95%CI 0.96-1.92]. Cumulative time trend analyses suggested an increase in the prevalence of diabetes among adults in urban West Africa, from approximately 3.0% (95%CI 1.0-7.0) to 4.0% (95%CI 2.0-9.0) in the past 10 years. The prevalence of inactivity in West Africa was 13% (95%CI 9.0-18.0). An association was found between physical inactivity and being older (> or = 50 years) (PR 1.82, 95%CI 1.36-2.44), female gender (PR 1.62, 95%CI 1.41-1.87) and urban residence (PR 2.04, 95%CI 1.58-2.63). CONCLUSIONS: Diabetes and physical inactivity are important public health issues in urban West Africa, with similar prevalences to wealthy industrialized countries. There is an urgent need for policy makers, politicians and health promotion experts to put measures in place to encourage active lifestyles and control diabetes in urban West Africa.